Could 'mini-brains' replace animal models in the lab?

Animal models for disease are an essential part of drug trials, at least for now. New research into a novel way of producing brain cells might lead to a more cost-effective and ethical way to test the drugs of the future.

The applications for the mini-brain cover almost the entirety of neuropharmacological research.Image credit: Dr. Thomas Hartung, Johns Hopkins Bloomberg School of Public Health

Animal trials are almost as old as medical science itself, but their history and usefulness does not prevent them from being a controversial topic.

Any possible routes to minimize their usage are unceasingly pursued.

Hundreds of thousands of animals are used for neurological research on a yearly basis. However, around 95% of drugs that show success in animals do not work in humans.

Researchers at Johns Hopkins Bloomberg School of Public Health, in Baltimore, MD, are hoping that their new mini-brains might eventually take over from standard animal-based neurological research.

The birth of the mini-brain

The Center for Alternatives to Animal Testing (CAAT) at Johns Hopkins have been at the forefront of cell culture methods for 35 years. Dr. Thomas Hartung and his team at CAAT are working to develop miniature brains consisting of genuine, functioning interconnected neurons.

Currently, human cell cultures consist of just one type of cell, and those cells are not interconnected in any way. The cells are often generated from either a resected tumor or embryonic stem cells, both of which carry their own ethical issues.

Dr. Hartung's groundbreaking mini-brains are cut from a different cloth. They are constructed using skin cells from healthy patients "reprogrammed" to become stem cells. As such, these cells, known as induced pluripotent stem cells (iPSCs), circumvent the ethical minefield.

The cells are genetically adapted to enter an embryonic stem cell-like state and stimulated to grow into brain cells.

Size, usage and practicality

It is hoped that these balls of cells will be useful for investigations into the etiology and treatment of many diseases, including Alzheimer's, Parkinson's and autism. Projects using the mini-brains to study viral infections, trauma and stroke, are already underway.

The mini-brains, just 350 µm across, consist of 10,000-20,000 individual brain cells. Around 100 of these identical groups of cells can easily be grown in a single petri dish. Unlike standard cell cultures, they contain a range of functioning, connected brain cells, including astrocytes and oligodendrocytes.

The mini-brains mimic the embryonic brain, and researchers are able to observe the nerve's myelin sheaths grow and watch as they develop spontaneous electrical signaling.

Dr. Hartung is applying to patent the mini-brains and has set up a company called ORGANOME to market and sell them to laboratories.

In any type of research, cost is always going to be a concern; Medical News Today asked Dr. Hartung how these miniature brains would financially compare to the use of existing mouse models. He said that "a price for the mini-brains has not been set, but will be in the rank order of a laboratory rat ($20-30)."

Of course, the cost of the rat itself is only a small part of the cost of an animal test. Dr. Hartung goes on to explain that "a developmental neurotoxicity study, for which our model is predestined, uses 1,400 rats and costs about $1.4 million for one substance." Making bad choices in drug trials can be incredibly costly.

The future of the mini-brain

The team hopes that the future of the mini-brain will be bright. The potential uses are legion and developments using new cell types will open the possibilities even wider.

By using skin cells from individuals with genetic diseases, researchers will be able to experiment on cell lines with specific genetic changes. Dr. Hartung believes the brains will be useful in research into illicit drugs, e-cigarettes, chemical threat agents and disease models of infection.

MNT asked whether the team planned on increasing the size of the brains in the future to add extra levels of complexity. Dr. Hartung said:

"The first problem is oxygen and nutrient supply in the center. We stop at a size where this is not limiting. Continuing brain development also leads to the formation of many structures, (making it) difficult to control.

Every mini-brain is then an individual. Our cell balls, after 10 weeks, are homogenous and identical, a big advantage for comparing substance effects."

The future of the mini-brain certainly seems bright. An easily replicable selection of identical neural cells, shipped to your lab for the price of a mouse. Perhaps this could spell the end for animal trials in neurological research.

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